BIBO3304 TFA

BIBO3304 TFA has subnanomolar affinity for both the human and the rat neuropeptide Y (NPY) Y1 receptor with IC50 values of 0.38±0.06 nM and 0.72±0.42 nM, respectively ^[1].

BIBO3304 TFA(10 µM, 24h) effectively blocked Geminin upregulation in 10% serum-cultured vascular smooth muscle cells (VSMC) induced by 200 nM NPY ^[2].

BIBO3304 TFA (5 µmol)-treated mice showed a significant increase in whole body bone mineral content after 4- and 8-weeks of treatment, and this effect was not observed in vehicle-treated mice ^[3]. BIBO3304 TFA treatment improved β-cell function and preserved functional β-cell mass, thereby resulting in better glycaemic control in both high-fat-diet/multiple low-dose streptozotocin- and db/db type 2 diabetic mice ^[4]. Periphery specific antagonism of Y1R signalling via the non-brain penetrable Y1R antagonist BIBO3304 TFA prevents diet-induced obesity via stimulating energy expenditure and whole-body thermogenesis ^[5].

References:
[1]. Wieland H A, Engel W, Eberlein W, et al. Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents[J]. British journal of pharmacology, 1998, 125(3): 549-555.
[2]. Jiang Z, Zhou Y, Chen X, et al. Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin[J]. Molecular and cellular biochemistry, 2017, 433(1): 205-211.
[3]. Sousa D M, Baldock P A, Enriquez R F, et al. Neuropeptide Y Y1 receptor antagonism increases bone mass in mice[J]. Bone, 2012, 51(1): 8-16.
[4]. Yang C H, Ann-Onda D, Lin X, et al. Elevated Neuropeptide Y1 Receptor Signaling Contributes to β-cell Dysfunction and Failure in Type 2 Diabetes[J]. bioRxiv, 2021.
[5]. Yan C, Zeng T, Lee K, et al. Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity[J]. Nature communications, 2021, 12(1): 1-20.